June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Sustained Prednisolone Acetate-loaded Microfilm Drug Delivery System Effectively Prolongs corneal allograft survival in the rat keratoplasty model
Author Affiliations & Notes
  • Yu-Chi Liu
    Singapore Eye Research Institute, Singapore, Singapore
    Singapore National Eye Centre, Singapore, Singapore
  • Yan Peng
    School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore
  • Nyein Chan Lwin
    Singapore Eye Research Institute, Singapore, Singapore
  • Subbu S Venkatraman
    School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore
  • Tina Wong
    Singapore Eye Research Institute, Singapore, Singapore
    Singapore National Eye Centre, Singapore, Singapore
  • Jodhbir Mehta
    Singapore Eye Research Institute, Singapore, Singapore
    Singapore National Eye Centre, Singapore, Singapore
  • Footnotes
    Commercial Relationships Yu-Chi Liu, None; Yan Peng, None; Nyein Chan Lwin, None; Subbu S Venkatraman, None; Tina Wong, 61, 250,006 (P); Jodhbir Mehta, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5058. doi:
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      Yu-Chi Liu, Yan Peng, Nyein Chan Lwin, Subbu S Venkatraman, Tina Wong, Jodhbir Mehta, ; Sustained Prednisolone Acetate-loaded Microfilm Drug Delivery System Effectively Prolongs corneal allograft survival in the rat keratoplasty model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5058.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

To investigate the efficacy of a sustained prednisolone acetate (PA)-loaded poly (d,l-lactide-co-ε-caprolactone) (PLC) microfilm drug delivery system (DDS) for promoting the survival of allogeneic rat corneal grafts after penetrating keratoplasty (PK).

 
Methods
 

A total of 48 PK were performed using Fisher rats (allogeneic groups) and Lewis rats (syngeneic group) as donors and Lewis rats as recipients: group 1 (n=12), syngeneic control; group 2 (n=12), allogeneic control without treatment; group 3 (n=12), allogeneic grafts with subconjunctivally-implanted PA-loaded microfilm treatment; group 4 (n=12): allogeneic grafts with 1% PA eye drops treatment. All grafts were evaluated for 28 days by a scoring rejection index (RI), assessing graft opacity, edema and neovascularization by slit lamp biomicroscopy and anterior segment optical coherence tomography (ASOCT). Time to rejection was analyzed with Kaplan-Meier survival analysis. PA concentrations in the aqueous humor were measured using high-performance liquid chromatography. Histopathological and immunohistochemical staining were also performed.

 
Results
 

The PA-loaded microfilms achieved a sustained and steady release at a rate of 7.0ug/day, with a consistent drug concentration of 207-209 ng/ml in the aqueous. The mean survival was >28 days in group 1, 9.9±0.8 days in group 2, 26.8±2.7 days in group 3 (P = 0.023 as compared with group 2), and 26.4±3.4 days in group 4 (P = 0.027 as compared with group 2). Statistically significant decrease in CD4+, CD8+, CD163+, CD11c+, CD 25+ and CD54+ cell infiltration in group 3 as compared with group 2 was observed on immunohistochemistry (P<0.001). There was no significant difference between group 3 and group 4 in the mean survival and immunohistochemical analysis.

 
Conclusions
 

The sustained PA-loaded microfilm DDS effectively prolongs corneal allograft survival in the rat model. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

 
 
Figure 1: Representative slit lamp biomicroscopy and ASOCT photos showing the status of the corneal grafts 2 and 4 weeks after penetrating keratoplasty
 
Figure 1: Representative slit lamp biomicroscopy and ASOCT photos showing the status of the corneal grafts 2 and 4 weeks after penetrating keratoplasty
 
 
Figure 2: Kaplan-Meier analysis of the rejection-free graft survival
 
Figure 2: Kaplan-Meier analysis of the rejection-free graft survival
 
Keywords: 487 corticosteroids  
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